The invention relates to a device and a method for picking up individual objects or particles and placing them in containers or cavities filled with liquid.
For picking up, transferring and placing objects or particles (pick-and-place operation) several methods are known.
If the objects to be picked up are comparatively huge and heavy, gripping devices are often used. In EP-A-0 671 351, for example, picking up and placing is realized by means of such gripping devices. The enormous technical demand and expenditure for their construction as well as the fact that it is difficult to miniaturize them is disadvantageous in these apparatuses.
In general, these disadvantages also occur if suction devices are used. DE-A-195 12 155 describes a pick-and-place machine in which particles can be transported as well as picked up and placed in chambers by means of vacuum technology. This device is moreover disadvantageous in that very complicated and expensive vacuum-stable parts are required.
As an alternative to these methods, often more economical adhesive devices are used for transporting and/or picking up, in particular for light objects. It is a disadvantage of conventional prior art methods that since the object has to be released from the adhesive surface after placing, e.g. by wiping off or spinning, it is difficult or impossible to exactly place the object. Moreover, remnants of the adhesive on the objects to be transported can be a hindrance. When being used several times, the adhesive force decreases so that it becomes necessary to replace the device or to renew the adhesive surface.
Examples for picking-up and transporting means in which adhesive surfaces are applied are DE-A-30 10 779, GB-A-2 237 001 or U.S. Pat. No. 5,470,116. It is a disadvantage of these devices that the objects have to be released manually. Automation and miniaturization is therefore impossible. Moreover, great demands are made on the adhesive because it must be strong enough that the object to be transported sticks thereon during transport; however, it must be easily possible to release the object.
A further example is disclosed in U.S. Pat. No. 5,553,344. In this device for picking up light objects a plurality of detachable sheets containing an adhesive material are used. After picking up the objects, the contaminated sheets are removed. This method is disadvantageous in that the adhesive surface must continuously be renewed. It is not intended to release the objects.
U.S. Pat. No. 5,637,395 discloses specific adhesives which allow a semiconductor wafer to be held during processing (e.g. cutting). The objects are released in that photopolymerizable compounds are added to the adhesive. After irradiation, the adhesion decreases and the wafer is released. It is a disadvantage of this invention that an expensive adhesive must be used.
U.S. Pat. No. 4,073,530 discloses a pick-up device having an adhesive surface on an end that can be flexibly shaped. The object is released by a reduction of this adhesive surface by means of a translatory movement. It is a disadvantage of this device that the shape and the weight of the object to be picked up must be such that a reduction of the adhesive surface is possible. This is not the case with round objects. It is also disadvantageous that it cannot be guaranteed that remnants of the adhesive are left on the object to be transported.
If the objects to be manipulated are small spherical and light particles, in particular synthesis resin beads, which are used in combinatorial solid-phase synthesis and high throughput screening, specific methods are disclosed which allow in particular the allocation of individual beads to wells or cavities of a microtitre plate.
WO-A-98/17383 describes the possibility of distributing a defined number of beads, which can be used in combinatorial synthesis, into a microtitre plate. However, the beads to be distributed are held in suspension. With this method it is not possible to transport individual particles. The used device needs pipette-like devices whose geometry makes a miniaturization more difficult.
WO-A-98/32000 discloses picking up individual beads and transferring them to a microtitre plate, wherein one bead each can be placed in a cavity of the microtitre plate. However, also in this case the beads are held in suspension and can thus not be selected individually. The bead is picked up by drawing up liquid until a bead blocks the inlet of the needle. A disadvantage of this method is the high demand placed on the apparatus due to the required pressure sensor means.
WO-A-98/08092 describes a method allowing the deposition of beads having essentially the same size and dimension into a predetermined grid such as a microtitre plate. For this purpose, the beads are filled in a capillary. An adhesive layer is used for fixing the beads. It is a disadvantage of this method that after allocation of the beads to individual fields the excess beads must be removed. Moreover, the allocation of the bead fields with respect to each other is predetermined. The beads in the arrays can only be transferred into the capillary system as a whole through the apertured mask. Thus, the beads cannot individually be transferred to cavities of a microtitre plate. Consequently, in principle only beads having the same size can be handled in this method. Moreover, the placement of adhesive droplets for forming an adhesive layer is relatively complicated and thus the process costs are comparatively high.
It is the object of the present invention to provide an improved device and an improved method for picking up small objects or particles and placing them in containers or cavities filled with liquid. The present invention particularly intends to overcome the above-mentioned disadvantages of the prior art. In particular, the device of the present invention and the method of the present invention should be suitable for handling synthesis beads being used in combinatorial solid-phase chemistry for drawing up combinatorial substance libraries. This object is achieved with the features of the claims.
In achieving this object, the invention starts out from the basic idea that prior to each transport operation of an object a surface of a transport means is provided with an adhesive substance, an adhesive layer or an adhesive (in the following simply xe2x80x9cadhesivexe2x80x9d) or at least the adhesion of a probably present adhesive is increased, wherein subsequently this surface is brought in contact with the object in order to transport it. For releasing the object from the transport means, the adhesion of the adhesive is reduced or the adhesive is essentially removed completely so that it is released from the transport means.
In the meaning of the present invention, the terms xe2x80x9ctransportxe2x80x9d and xe2x80x9ctransferxe2x80x9d mean the re-positioning of an object from a starting or picking-up position to an end or placing position. These terms are not restricted to any direction.
In a preferred embodiment of the present invention a respective method comprises in particular the following steps:
(a) One end of a means suitable for the transport operation, such as a rod or a pin, is immersed into an adhesive liquid or a liquid comprising adhesive substances. The end of the means is constructed such that when being brought in contact with the objects to be transported, it has a suitably large common surface, i.e. adhesive surface.
(b) After removal from the liquid, the adhesive surface is optionally dried in order to allow the adhesive substances contained in the liquid to concentrate. For example, this can be done by simply leaving it in the air.
(c) Parts of the transport means having an adhesive surface are brought in contact with the object to be transported in such a way that the object can be lifted and transferred or transported.
(d) The object is placed in a container filled with liquid or at least one cavity filled with liquid, wherein the adhesive surface between the object to be transported and the transport means is preferably removed by the liquid or at least, however, the adhesion of the adhesive is reduced considerably so that the object is released from the transport means. For example, this can be done by preparing a mixture or solution. The object is thus allowed to enter the container or cavity.
(e) After the object was released, the process can be repeated as often as required.
Adhesive liquids can, for example, be viscous compounds such as polyethylene glycols or polypropylene glycols. Examples for liquids containing adhesive substances are aqueous sugar solutions (e.g. glucose, saccharose, maltose) or concentrated saline solutions.
Liquids by means of which the objects can be released can, for example, be water, aqueous buffer or saline solutions or organic solvents or separating reagents whichxe2x80x94in case synthesis beads are the objects to be transportedxe2x80x94simultaneously allow the separation of compounds adhering to the beads.